scholarly journals Combination Therapy in Moderate to Severe Alzheimer’s Disease - Overview and Discussion Points for the Future

2011 ◽  
Vol 6 (4) ◽  
pp. 228
Author(s):  
José L Molinuevo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combination Therapy ◽  
Receptor Antagonist ◽  
Cholinesterase Inhibitors ◽  
Current Data ◽  
Aspartate Receptor ◽  
The Future

Two effective symptomatic therapies are available for Alzheimer’s disease: the cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-D-aspartate receptor antagonist. Current data demonstrate that combination therapy with memantine and a ChEI produces symptomatic benefits in all domains of AD. The benefits of combination therapy are greater than those of ChEI monotherapy, are sustained long term and appear to increase with time.

scholarly journals Alzheimer’s Disease: Current and Future Treatments. A Review

2014 ◽  
Vol 2 (2) ◽  
pp. 56-63
Author(s):  
Evelyn Chou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Nmda Antagonists ◽  
Disease Modifying Drugs ◽  
Plaque Deposition ◽  
The Future ◽  
Disease Modifying ◽  
Future Treatments

Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder whose treatment poses a big challenge. Proposed causes of AD include the cholinergic, amyloid and tau hypotheses. Current therapeutic treatments have been aimed at dealing with the neurotransmitter imbalance. These include cholinesterase inhibitors and N-Methyl-D-aspartate (NMDA) antagonists. However, current therapeutics have been unable to halt AD progression. Much research has gone into the development of disease-modifying drugs to interfere with the course of the disease. Approaches include secretase inhibition and immunotherapy aimed at reducing plaque deposition. However, these have not been successful in curing AD as yet. It is believed that the main reason why therapeutics have failed to work is that treatment begins too late in the course of the disease. The future of AD treatment thus appears to lie with prevention rather than cure. In this article, current therapeutics and, from there, the future of AD treatment are discussed.

scholarly journals New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer’s disease: focus on brexpiprazole and pimavanserin

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 686 ◽  
Author(s):  
Filippo Caraci ◽  
Mario Santagati ◽  
Giuseppe Caruso ◽  
Dario Cannavò ◽  
Gian Marco Leggio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Receptor Antagonist ◽  
Safety Profile ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Phase Iii ◽  
Second Generation Antipsychotics ◽  
Recent Phase

Behavioral and psychological symptoms of dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety, psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for Alzheimer’s disease (AD) and are common precipitants of institutional care. Agitation and psychosis are associated with accelerated disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation antipsychotics for the treatment of agitation and psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new antipsychotic drugs with improved efficacy and safety are needed as an alternative to current antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and psychosis in AD and focus on the recent positive clinical evidence observed with two new antipsychotics drugs: brexpiprazole and pimavanserin. Brexpiprazole is a receptor partial agonist (D2, D3, 5-HT1A), receptor antagonist (5-HT2A/B, α1B/α2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation antipsychotics. Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for psychosis occurring in Parkinson’s disease. Recent phase II studies suggest that this drug is effective in AD patients with more severe psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of pimavanserin for the treatment of psychosis in AD.

Cognitive Enhancers in Moderate to Severe Alzheimer's Disease

2011 ◽  
Vol 3 ◽  
pp. CMT.S6344 ◽  
Author(s):  
Rüdiger Hardeland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Routes Of Administration ◽  
Aspartate Receptor ◽  
Oral Formulations ◽  
Investigational Drugs ◽  
Hybrid Molecules ◽  
Copper Zinc ◽  
Mental Decline

The treatment of moderate to severe Alzheimer's disease is reviewed with regard to mechanisms of action, pharmacokinetics, metabolism, safety/tolerability, and efficacy in reducing cognitive, behavioral/psychiatric, functional and global symptoms. The cholinesterase inhibitors donepezil, rivastigmine and galantamine and the N-methyl-d-aspartate receptor channel blocker memantine are moderately beneficial. Small improvements over a few months are followed by slowed mental decline. Concerning cognitive, functional and global functions, these drugs are similarly effective. Cholinesterase inhibitors also reduce apathy, memantine counteracts agitation and aggression. Serious adverse effects are rare with all four drugs. Cholinesterase inhibitors bear a risk for patients with cardiac diseases. Adverse emetic events are typical for oral formulations of these drugs, but less for rivastigmine transdermal patches. Other routes of administration and use of a galantamine prodrug are currently investigated. The superiority of combination therapies over monotherapies requires further support. Promising investigational drugs include the copper/zinc ionophore PBT2 and multifunctional hybrid molecules.

scholarly journals Psychosis in Alzheimer’s Disease

2020 ◽  
Vol 20 (12) ◽  
Author(s):  
Clive Ballard ◽  
Helen C. Kales ◽  
Constantine Lyketsos ◽  
Dag Aarsland ◽  
Byron Creese ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Atypical Antipsychotics ◽  
Cholinesterase Inhibitors ◽  
Pharmacological Treatments ◽  
Muscarinic Agonists ◽  
Pharmacological Management ◽  
Psychological Therapies ◽  
New Treatment

Abstract Purpose of Review To review the incidence, treatment and genetics of psychosis in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Recent Findings Psychosis in Alzheimer’s disease (AD) has an incidence of ~ 10% per year. There is limited evidence regarding psychological interventions. Pharmacological management has focused on atypical antipsychotics, balancing modest benefits with evidence of long-term harms. The 5HT2A inverse agonist pimavanserin appears to confer benefit in PD psychosis with initial evidence of benefit in AD. Cholinesterase inhibitors give modest benefits in DLB psychosis. The utility of muscarinic agonists, lithium, glutamatergic and noradrenergic modulators needs further study. Summary Recent work has confirmed the importance of psychosis in MCI as well as AD. The lack of evidence regarding psychological therapies is an urgent knowledge gap, but there is encouraging evidence for emerging pharmacological treatments. Genetics will provide an opportunity for precision medicine and new treatment targets.

scholarly journals Combination pharmacotherapy in Alzheimer's disease

2003 ◽  
Vol 5 (3) ◽  
pp. 299-305
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combination Therapy ◽  
Synergistic Effects ◽  
Current Therapy ◽  
Combination Drug ◽  
Term Care ◽  
Available Information ◽  
Individual Efficacy

Alzheimer's disease is a progressive, debilitating form of dementia affecting more than 18 million people worldwide. Without a cure, many patients and their families must turn to long-term care institutions during the later stages of the disease. Our current treatments only delay progression and help control behavioral symptoms. In recent years, research within this field has expanded to include many clinical trials on potential drug therapies. However, despite the numerous studies, the enigma of this disease remains. It is difficult yet necessary, to stay abreast of emerging information that may warrant changes in current therapy. Rationale for combination therapy becomes evident as we review the multiple neurochemical pathways common to the disease. This paper will review available information on Alzheimer's disease pharmacotherapy, and evaluate data on the use of combination drug therapy. Individual efficacy, possible synergistic effects, and the safety of combination therapy will also be addressed.

scholarly journals Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease

2013 ◽  
Vol 9 (6) ◽  
pp. 733-740 ◽  
Author(s):  
Carolyn W. Zhu ◽  
Elayne E. Livote ◽  
Nikolaos Scarmeas ◽  
Marilyn Albert ◽  
Jason Brandt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Outcomes ◽  
Cholinesterase Inhibitors

Cholinesterase Inhibitors and Memantine

2008 ◽  
Author(s):  
Constantine G. Lyketsos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Imaging Study ◽  
Behavioral Symptoms ◽  
Cognitive Symptoms ◽  
Dementia Patients ◽  
Comparison Groups

Several lines of evidence suggest that acetylcholine (ACh) neurotransmission is important to the normal functioning of memory, and loss of ACh-producing cells in the basal forebrain (nucleus basalis) is a consistent finding in patients with Alzheimer’s disease and other dementias. The most successful approach to increasing ACh in vivo has been to develop drugs that reduce its degradation by the synaptic enzyme acetylcholinesterase (AChE). Four cholinesterase inhibitors are available to treat memory and other cognitive symptoms in dementia patients. They may also stabilize or prevent the onset of milder non-cognitive neuropsychiatric or behavioral symptoms, although their use as exclusive agents for the more severe forms of the latter is not recommended. A recent Consensus Panel has articulated sound clinical principles regarding the use of these drugs in the context of the broader treatment of Alzheimer’s dementia (Lyketsos et al., 2006). Tacrine, donepezil, rivastigmine, and galantamine have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease. Tacrine should not ordinarily be used in light of the associated high risk of hepatotoxicity, its complex titration, and the availability of bettertolerated alternatives. The other three cholinesterase inhibitors seem similar in efficacy. All appear to modestly improve cognitive symptoms in 15% to 20% of patients, sometimes quite notably. In addition, they may either improve patient function and delay the emergence of behavioral symptoms or reduce the severity of the latter. The evidence does not support their use as single agents to treat more severe neuropsychiatric symptoms such as depression or delusions, although patients with apathy and visual hallucinations may respond. Any benefit of cholinesterase inhibitors to the long-term progression of dementia has not been shown conclusively. Some studies suggest that they may attenuate the long-term slope of cognitive or functional decline, but those studies have been flawed due to high levels of dropout and the use of historical untreated comparison groups. One brain imaging study, part of a clinical trial, has suggested that they may affect the size of the hippocampus or the integrity of hippocampal neurons. In the absence of replication or a better understanding of the imaging measures involved, these data are not conclusive.

Behavioral and Neuropsychiatric Outcomes in Alzheimer's Disease

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S18) ◽  
pp. 22-25 ◽  
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Psychological Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Caregiver Distress ◽  
Aspartate Receptor ◽  
Home Placement ◽  
Behavioral And Psychological Symptoms

AbstractBehavioral and psychological symptoms of dementia pose significant challenges in the management of patients with Alzheimer's disease. Neuropsychiatric symptoms are associated with cognitive decline, highly impaired activities of daily living, and frontal lobe pathology. Moreover, behavioral and psychological symptoms can diminish patient quality of life, increase caregiver distress, and accelerate nursing home placement. Although these symptoms are often associated with the later stages of Alzheimer's disease, a high percentage of individuals with mild cognitive impairment or mild Alzheimer's report symptoms as well. This article provides an overview of behavioral and neuropsychiatric symptoms associated with Alzheimer's disease and discusses nonpharmacologic and pharmacologic approaches to the management of such symptoms. For patients with severe behavioral and psychological symptoms of dementia, pychotropic agents may be warranted, whereas approved therapies for Alzheimer's, including cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine, may be appropriate in less severe cases.

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